Sex differences in symptoms following the administration of BNT162b2 mRNA COVID-19 vaccine in children below 5 years of age in Germany (CoVacU5): a retrospective cohort study.

ABSTRACT

BACKGROUND: Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. METHODS: This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. RESULTS: The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5-10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI] 1.15-1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI 1.01-1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR 0.29, 95% CI 0.11-0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. CONCLUSIONS: Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID DRKS00028759).

For many childhood vaccines, the immune responses are different between the sexes. For the COVID-19 vaccine BNT162b2, the symptoms occurring after vaccination in children have not sufficiently been investigated. In this study, we performed an analysis of a dataset of retrospectively collected information on symptoms occurring after vaccinations with BNT162b2 and regular childhood vaccines in 7801 children under the age of 5 years in Germany, with a focus on the sex differences. Among the four categories assessed, local injection-site and general symptoms were more frequent in girls compared to boys. In contrast, following the administration of other childhood vaccines, the caregivers more frequently reported muscle-related symptoms in boys than in girls. In conclusion, sex differences exist in symptoms occurring after vaccinations even in young children, which is important to consider for future studies evaluating vaccine safety.